This is a program-project for the genetic study of mammalian regulatory mechanisms. Genetic variants in mice exhibiting altered regulation of specific gene products are analyzed to determine the molecular basis of the regulatory mechanisms involved and characterized genetically to determine the location, and characteristics (recessive/dominant/additive and cis/trans expression) of the gene responsible. Additionally, recombinant DNA technology is being applied to clone an examine the relevant DNA sequences. Some of the major systems under study include factors regulating beta-glucuronidase synthesis and expression, cell membrane receptors and H2 surface antigen, X chromosome structural genes for the study of X inactivation; biogenesis of lysosomes; DNA sequences corresponding to abundant mRNA; and the use of both protein and nucleic acid sequence variation in mapping the mouse genome.